The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Diagnostic and discriminative accuracy of plasma phosphorylated tau 217 for symptomatic Alzheimer's disease in a Chinese cohort.","authors":"Li-Min Li, Ping Che, Dequan Liu, Yu Wang, Jia Li, Dian He, Tao Liu, Nan Zhang","doi":"10.1016/j.tjpad.2025.100092","DOIUrl":"10.1016/j.tjpad.2025.100092","url":null,"abstract":"<p><strong>Background: </strong>Plasma phosphorylated tau at threonine 217 (p-tau217) measured with an ultrasensitive immunoassay method has been demonstrated to be an optimal biomarker for Alzheimer's disease (AD).</p><p><strong>Objectives: </strong>The aim of this study was to establish the reference interval for plasma p-tau217 in Chinese individuals and evaluate its diagnostic value in symptomatic AD.</p><p><strong>Design, setting, participants: </strong>We recruited 150 cognitively unimpaired (CU) individuals, 60 patients with AD dementia, 30 patients with mild cognitive impairment (MCI) due to AD, 40 patients with frontotemporal lobar degeneration (FTLD), and 70 patients with subcortical ischaemic vascular dementia (SIVD).</p><p><strong>Measurements: </strong>The concentrations of plasma p-tau217, total tau, amyloid-beta (Aβ)42 and Aβ40 were measured with a single-molecule array.</p><p><strong>Results: </strong>Plasma p-tau217 outperformed other biomarkers in discriminating AD patients from CU controls, FTLD patients, and SIVD patients (AUC = 0.983, 0.936, 0.892) and discriminating MCI patients from CU controls (AUC = 0.943). The plasma p-tau217 level was negatively correlated with memory in patients with symptomatic AD.</p><p><strong>Conclusion: </strong>The diagnostic accuracy of plasma p-tau217 was exceptional for AD, even at early stages, in the Chinese population.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100092"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The disease burden, risk factors and future predictions of Alzheimer's disease and other types of dementia in Asia from 1990 to 2021.","authors":"Jinxuan Guo, Pin Wang, Jin Gong, Wenxian Sun, Xiaodong Han, Chang Xu, Aidi Shan, Xin Wang, Heya Luan, Shaoqi Li, Ruina Li, Boye Wen, Runqi Chen, Sirong Lv, Cuibai Wei","doi":"10.1016/j.tjpad.2025.100122","DOIUrl":"10.1016/j.tjpad.2025.100122","url":null,"abstract":"<p><strong>Background: </strong>There is a lack of analysis and prediction of the disease burden of Alzheimer's disease and other dementias (ADOD) in Asia.</p><p><strong>Objectives: </strong>This study aims to explore the impact of ADOD on the Asian region during the period from 1990 to 2021.</p><p><strong>Design: </strong>Data on ADOD in Asia from 1990 to 2021 were collected from the Global Burden of Disease (GBD) Study 2021. We analyzed the number and age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of ADOD from 1990 to 2021. Joinpoint regression analysis was performed, and the average annual percent changes (AAPCs) were calculated to evaluate the trends during this period. Subsequently, an auto - regressive integrated moving average (ARIMA) prediction model analysis was conducted to assess the trends in the next 30 years, aiming to report the epidemiology and disease burden of ADOD in Asia.</p><p><strong>Results: </strong>According to the analysis of the GBD database in 2021, the deaths, DALYs, incidence, and prevalence of ADOD increased by 297.34 %, 249.54 %, 244.73 %, and 250.44 % in Asia from 1990 to 2021. The ASRs of incidence, prevalence, death, and DALYs in both males and females, which consistently increased over the study period, showed that the ASRs of all females were consistently higher than those of males in Asia from 1990 to 2021. During the period from 1990 to 2021, Qatar and the United Arab Emirates witnessed the greatest changes in the number of DALYs, incidence, and prevalence. Afghanistan and China had the highest age-standardized mortality rate (ASMR) in 2021. It is worth noting that high fasting blood glucose is the top risk factor for the onset of ADOD. Females are more susceptible to the risk factor of high body-mass index (BMI), while males are more likely to be affected by smoking. According to the analysis of the ARIMA prediction model, the disease burden of ADOD in Asia will continue to show an upward trend in the next 30 years.</p><p><strong>Conclusions: </strong>We should pay attention to the issue of population aging, attach importance to the intervention measures targeting the risk factors of ADOD, and formulate action plans to address the rising incidence of ADOD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100122"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell RNA sequencing and mendelian randomization analysis reveal the potential role of synaptic vesicle cycling-related genes in Alzheimer's disease.","authors":"Junfeng Zeng, Ruihua Zhang, Huihua Xu, Chengwu Zhang, Li Lu","doi":"10.1016/j.tjpad.2025.100097","DOIUrl":"10.1016/j.tjpad.2025.100097","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) involves alterations in synaptic vesicle cycling (SVC), which significantly affect neuronal communication and function. Therefore, a thorough investigation into the potential roles of SVC-related genes (SVCRGs) in AD can enhance the identification of critical biomarkers that may influence disease progression and treatment responses.</p><p><strong>Methods: </strong>The datasets used in this study were sourced exclusively from public databases. By integrating differential expression analysis with Mendelian randomization (MR), we identified SVCRGs as biomarkers for AD. Functional characterization of these biomarkers was performed, followed by integration into a nomogram. Further investigation of immune infiltration in AD patients and healthy individuals was carried out. Ultimately, the potential cellular mechanisms of AD were explored through single-cell RNA sequencing (scRNA-seq) analysis.</p><p><strong>Results: </strong>ATP6V1D, ATP6V1G2, CLTB, and NSF were identified as biomarkers, exhibiting a positive correlation with each other and a downregulated expression in AD. These markers were pinpointed as protective factors for AD [odds ratio (OR) < 1, P < 0.05], with potential to reduce the risk of the disease. Integrated into a nomogram, they demonstrated satisfactory diagnostic performance and clinical utility, surpassing the use of single gene. They were collectively enriched in pathways related to \"interferon gamma response\", \"inflammatory response\", and \"TNFα signaling via NFκB\". Additionally, an increase in infiltration of 17 immune cell types in AD was noted, particularly cells associated with neuroinflammation such as activated CD8 T cells and various dendritic cells (DCs), suggesting an inflammatory milieu in AD while also displaying a negative correlation with the biomarkers. The cell types were further annotated, revealing specific expressions of biomarkers and uncovering the heterogeneity of excitatory neurons. A significant reduction in the overall number of excitatory neurons under AD conditions was observed, alongside consistent expression of biomarkers during the developmental stages of excitatory neurons.</p><p><strong>Conclusion: </strong>By using MR, we firstly identified four SVCRGs as protective factors for AD, functioning through pathways associated with mitochondrial dysfunction, chronic inflammation, immune dysregulation, and neuronal damage. These genes had the potential to modulate immune cell infiltration activated in AD patients and exhibited cell-type-specific expression profiles within AD-related cellular contexts. Their findings provide novel insights and valuable references for future research on AD pathogenesis and therapeutic strategies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100097"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct trajectories of subjective cognitive decline before diagnosis of neurocognitive disorders: Longitudinal modelling over 18 years.","authors":"Tau Ming Liew","doi":"10.1016/j.tjpad.2025.100123","DOIUrl":"10.1016/j.tjpad.2025.100123","url":null,"abstract":"<p><strong>Background: </strong>Subjective cognitive decline (SCD) is an established predictor of neurocognitive disorders (NCD) (i.e. mild cognitive impairment and dementia). Yet, its construct remains contentious. Many individuals with SCD do not progress to NCD, leading to an alternative term in the literature - 'functional cognitive disorders' - to describe the SCD experience in these individuals.</p><p><strong>Objectives: </strong>To examine the distinct differences in trajectories of SCD between those who did and did not eventually develop NCD.</p><p><strong>Design: </strong>Case-control study.</p><p><strong>Setting: </strong>Alzheimer's Disease Centers across USA.</p><p><strong>Participants: </strong>A total of 5,167 participants aged ≥50 years were followed up near-annually to evaluate for SCD and NCD (median follow-up=8.1 years; range=1.0-18.0). Cases were defined as those who developed incident NCD during follow-up; controls completed ≥10 years of follow-up and had normal cognition throughout follow-up period.</p><p><strong>Measurements: </strong>SCD was evaluated with a yes/no question based on \"perceived decline in memory relative to previously attained abilities\". The trajectories of SCD were modelled with mixed-effect logistic regression, using a backward timescale.</p><p><strong>Results: </strong>Those who developed NCD (cases) had new onset of SCD within past 20 years, which became particularly noticeable 13-14 years before diagnosis, and became even more evident in the last 4 years. Those who did not develop NCD (controls) reported SCD since younger age, with the probability of SCD remaining constant over time. The distinctive trajectories were consistent across Alzheimer's and non-Alzheimer's disease, and among those with higher baseline rates of SCD due to psychiatric conditions.</p><p><strong>Conclusions: </strong>SCD exhibits distinctive trajectories among those who do and do not progress to NCD. These distinctive trajectories can inform NCD risk for early interventions, and guide public health messaging to distinguish high-risk SCD from normal ageing. Future SCD scales may possibly need to evaluate symptom changes over a longer, 20-year horizon to better capture the new onset of SCD within this longer timeframe.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100123"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting cognitive decline: Deep-learning reveals subtle brain changes in pre-MCI stage.","authors":"Ling Yue, Yongsheng Pan, Wei Li, Junyan Mao, Bo Hong, Zhen Gu, Mingxia Liu, Dinggang Shen, Shifu Xiao","doi":"10.1016/j.tjpad.2025.100079","DOIUrl":"10.1016/j.tjpad.2025.100079","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mild cognitive impairment (MCI) and preclinical MCI (e.g., subjective cognitive decline, SCD) are considered risk states of dementia, such as Alzheimer's Disease (AD). However, it is challenging to accurately predict conversion from normal cognition (NC) to MCI, which is important for early detection and intervention. Since neuropathological changes may have occurred in the brain many years before clinical AD, we sought to detect the subtle brain changes in the pre-MCI stage using a deep-learning method based on structural Magnetic Resonance Imaging (MRI).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To discover early structural neuroimaging changes that differentiate between stable and progressive cognitive status, and to establish a predictive model for MCI conversion.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting and participants: &lt;/strong&gt;We first created a unique deep-learning framework for pre-AD conversion prediction through the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) database (n = 845). Then, we tested the model on ADNI-2 (n = 321, followed 3 years) and our private study (n = 109), the China Longitudinal Aging Study (CLAS), to validate the rationality for pre-MCI conversion prediction. The CLAS is a 7-year community-based cohort study in Shanghai. Our framework consisted of two steps: 1) a single-ROI-based network (SRNet) for identifying informative regions in the brain, and 2) a multi-ROI-based network (MRNet) for pre-AD conversion prediction. We then utilized these \"ROI-based deep learning\" neural networks to create a composite score using advanced algorithm-building. We coined this score as the Progressive Index (PI), which serves as a metric for assessing the propensity of AD conversion. Ultimately, we employed the PI to gauge its predictive capability for MCI conversion in both ADNI-2 and CLAS datasets.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;We primarily utilized baseline T1-weighted MRI scans to identify the most discriminative brain regions and subsequently developed the PI in both training and validation datasets. We compared the PI across different cognitive groups and conducted logistic regression models along with their AUCs, adjusting for education level, gender, neuropsychological test scores, and the presence of comorbid conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We trained the SRNet and MRNet using 845 subjects from ADNI-1 with baseline MRI data, in which AD and progressive MCI (converting to AD within 3 years) patients were considered as positive samples, while NC and stable MCI (remaining stable for 3 years) subjects were considered as negative samples. The convolutional neural networks identified the top 10 regions of interest (ROIs) for distinguishing progressive from stable cases. These key brain regions included the hippocampus, amygdala, temporal lobe, insula, and anterior cerebellum. A total of 321 subjects from ADNI-2, including 209 NC (18 progressive NC (pNC), 113 stable NC (sNC), and 78 remain","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100079"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donanemab: Appropriate use recommendations.","authors":"G D Rabinovici, D J Selkoe, S E Schindler, P Aisen, L G Apostolova, A Atri, S M Greenberg, S B Hendrix, R C Petersen, M Weiner, S Salloway, J Cummings","doi":"10.1016/j.tjpad.2025.100150","DOIUrl":"10.1016/j.tjpad.2025.100150","url":null,"abstract":"<p><p>Donanemab (Kisunla®), an IgG1 monoclonal antibody targeting N-terminal pyroglutamate-modified forms of amyloid-β, is approved in the United States for treatment of early symptomatic Alzheimer's disease (AD). Appropriate Use Recommendations (AUR) were developed to guide the implementation of donanemab in real-world practice, prioritizing safety considerations and opportunity for effectiveness. The AUR were developed by the AD and Related Disorders Therapeutic Workgroup by consensus, integrating available data and expert opinion. Appropriate candidates for donanemab treatment include persons with mild cognitive impairment or mild dementia due to AD (Clinical Stages 3-4, MMSE 20-30) who have biomarker confirmation of AD pathology by PET or CSF. Tau PET is not required for eligibility. Apolipoprotein E (APOE) genotyping should be performed prior to treatment to inform an individual's risk of developing Amyloid-Related Imaging Abnormalities (ARIA). Pre-treatment MRI should be obtained no more than 12 months prior to treatment. Patients with findings of >4 cerebral microbleeds, cortical superficial siderosis or a major vascular contribution to cognitive impairment should be excluded from treatment. The decision to initiate therapy should be grounded in a shared decision-making process that emphasizes the patient's values and goals of care. Donanemab is administered as a monthly intravenous infusion. Surveillance MRIs to evaluate for ARIA should be performed prior to the 2nd, 3rd, 4th and 7th infusions, prior to the 12th dose in higher risk individuals, and at any time ARIA is suspected clinically. Clinicians may consider discontinuing treatment if amyloid clearance is demonstrated by amyloid PET, typically obtained 12-18 months after initiating treatment.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100150"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy and safety of anti-amyloid monoclonal antibody versus acetylcholinesterase inhibitor with an in-depth analysis across genotypes and disease stages: a systematic review and meta-analysis.","authors":"Chih-Wei Hsu, Tien-Wei Hsu, Yu-Chen Kao, Yu-Hsuan Lin, Trevor Thompson, Andre F Carvalho, Brendon Stubbs, Ping-Tao Tseng, Fu-Chi Yang, Chia-Kuang Tsai, Chia-Ling Yu, Yu-Kang Tu, Chih-Sung Liang","doi":"10.1016/j.tjpad.2025.100195","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100195","url":null,"abstract":"<p><strong>Background: </strong>To date, studies have not compared the efficacy and safety of monoclonal antibodies (mABs) with acetylcholinesterase inhibitors (AChEIs).</p><p><strong>Methods: </strong>Five electronic databases were systemic searched from inception to 10 November 2024 for double-blinded randomized controlled trial (RCT) of patients diagnosed with MCI or mild AD treated with mABs or AChEIs for at least 6 months. The primary outcome was change in cognitive function, measured by the Alzheimer's Disease Assessment Scale-cognitive subscale 14-item (ADAS-Cog) and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SOB). The secondary outcomes were acceptability, tolerability, serious adverse events (SAE), and all -cause mortality. For mABs, amyloid-related imaging abnormalities-edema (ARIA-E), and amyloid-related imaging abnormalities-hemorrhage (ARIA-H) were also assessed. Subgroup analyses included (i) MCI versus mild AD; (ii) with versus without concomitant AD medications; and (iii) Apolipoprotein E (ApoE4) carriers versus non-carriers. Data were pooled using a random effects model within a Bayesian framework.</p><p><strong>Results: </strong>There were 8010 participants (mean age: 71.5 years) across seven mAB trials, and 4993 participants (mean age:70.7 years) in nine AChEI trials. When compared to placebo, only mABs, not AChEIs, were associated with a slower progression of cognitive decline on CDR-SOB (mean difference -0.41 (95 % credible interval -0.61 to -0.22); minimally important difference (MID) -1) and ADAS-Cog (-1.35 (-2.36 to -0.36), MID -2); however, these benefits of mABs did not reach MID across the two cognitive measurements. Besides, mABs were associated with a slower progression of cognitive decline on CDR-SOB (-0.30 (-0.60 to -0.001)) than AChEIs, although mABs and AChEIs did not differ across safety outcomes, including acceptability, tolerability, SAE, and all-cause mortality. Further analysis of mABs indicated that their efficacy did not differ by disease stage, concomitant AD medications, or APOE4 carrier status. However, APOE4 homozygotes carriers were associated with a 5.53-fold (2.48 to 13.07) increased odds of developing ARIA-E compared to non-carriers. Finally, lecanemab demonstrated relatively better efficacy and a more favorable profile on ARIA-E compared to aducanumab and donanemab.</p><p><strong>Conclusions: </strong>mABs were associated with a slower progression of cognitive decline than AChEIs; however, this effect did not reach the MID. The incidence of ARIA-E with mABs was associated with APOE4 carrier status and was not indicative of treatment efficacy.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100195"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of physical activity and lung function on cognitive health in older adults: Joint association and mediation analysis.","authors":"Peng Hu, Dan Song, Tian Heng, Ling-Ling Yang, Chuan-Chuan Bai, Rui He, Tao Liu, Ya-Xi Luo, Xiu-Qing Yao","doi":"10.1016/j.tjpad.2025.100090","DOIUrl":"10.1016/j.tjpad.2025.100090","url":null,"abstract":"<p><strong>Background: </strong>Maintaining cognitive health in old adults has become a significant public health challenge, with lung function and physical activity (PA) as essential modifiable factors. However, the joint and mediation effects of these two factors with cognition remain unclear.</p><p><strong>Objectives: </strong>This study assesses the joint association and mediation effects of lung function and PA with cognition.</p><p><strong>Design, setting, and participants: </strong>We utilized cross-sectional data from the 2011-2012 U.S. National Health and Nutrition Examination Survey, including adults aged 60-79 assessed for lung function, PA, and cognition.</p><p><strong>Main outcomes and measures: </strong>Lung function included forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), peak expiratory flow (PEF) and FEV₁/FVC. PA was assessed using the Global Physical Activity Questionnaire, covering occupational PA (OPA), transportation-related PA (TPA), and leisure-time PA (LTPA). Cognition was evaluated using the Digit Symbol Substitution Test, Animal Fluency Test, Delayed Recall Test and Immediate Recall Test. Weighted multiple linear regression models were used to analyze the separate and joint associations of lung function and PA with cognition, while also exploring potential mediation effects between these factors.</p><p><strong>Results: </strong>A total of 927 participants, representing 35,525,782 U.S. residents, were included, with a weighted median age of 65 (IQR, 63 -71) years, and 53.6 % were female. The results showed a significant positive association between lung function and cognitive function, with FEV₁, FVC, and PEF all positively correlated, while the FEV₁/FVC showed no notable link. Further analysis revealed the best cognitive performance observed in participants with active LTPA and the highest quartile of lung function, indicating a joint association of LTPA and lung function with cognition. Mediation analysis indicated that lung function mediated 24.1 % (95 %CI: 6.3 % - 47.0 %, P = 0.03) of the relationship between LTPA and cognition, while cognition mediated 10.2 % (95 %CI: 0.5 % - 27.0 %, P = 0.04) of the relationship between LTPA and lung function.</p><p><strong>Conclusion: </strong>Lung function and cognition may have a bidirectional relationship. The combination of active LTPA and better lung function was strongly associated with higher cognition, highlighting the need to strengthen exercise focused on lung function to maintain cognitive health in older adults.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100090"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular-kidney-metabolic syndrome and incidence of dementia among older adults.","authors":"Xiaqing Jiang, Amber L Bahorik, Christina S Dintica, Kristine Yaffe","doi":"10.1016/j.tjpad.2025.100112","DOIUrl":"10.1016/j.tjpad.2025.100112","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular-Kidney-Metabolic Syndrome (CKM) has profound impacts on cardiovascular events and mortality, yet its association with dementia risk remains poorly understood.</p><p><strong>Objectives: </strong>To investigate associations between CKM and dementia risk.</p><p><strong>Design: </strong>The prospective cohort study is within the Health, Aging, and Body Composition study, which enrolled participants from 1997 to 1998, with a 15-year follow-up for incident dementia.</p><p><strong>Setting: </strong>The population-based study took place in two US communities in Memphis, Tennessee, and Pittsburgh, Pennsylvania.</p><p><strong>Participants: </strong>Of the 3,075 participants aged 70 to 79 years initially enrolled, 14 were excluded for lacking baseline cognitive assessment, 308 for baseline cognitive impairment, 4 for missing follow-up, and 108 for missing CKM data, resulting in 2,641 in the analysis.</p><p><strong>Measurements: </strong>CKM staging, as defined recently by the American Heart Association framework, was based on constructs comprising dysfunctional adiposity, metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dementia was identified using hospital records, prescriptions for dementia medication, and a test of global cognition. Adjusted Cox and Fine-Gray proportional hazards models were used to estimate dementia risk and account for competing risk of death.</p><p><strong>Results: </strong>The 2,641 participants had a mean (SD) age of 74 (2.8) years at baseline; 53 % were female, 36 % were of Black race, and had a range of baseline CKM: 3 % Stage 0 (no CKM), 4 % Stage 1 (excess/dysfunctional adiposity), 26 % Stage 2 (metabolic risk factors), 24 % Stage 3 (subclinical CVD and CKD), and 43 % Stage 4 (clinical CVD and CKD). Compared to participants with CKM Stages 0-2, those with CKM Stages 3-4 had a 50 % increase in dementia risk (hazard ratio 1.50, 95 % CI 1.20 to 1.86) in the fully adjusted model. The association remained significant after additional adjustment for metabolic risk factors, CVD, and CKD, both separately and together. Accounting for competing risk of death yielded similar results.</p><p><strong>Conclusions: </strong>Among community-dwelling older adults, advanced CKM is associated with an increased risk of dementia. Older adults with CKM may need to be followed closely for adverse cognitive outcomes, and modifiable risk factors should be managed proactively.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100112"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarity AD: Asian regional analysis of a phase III trial of lecanemab in early Alzheimer's disease.","authors":"Christopher Chen, Sadao Katayama, Jae-Hong Lee, Jun-Young Lee, Masaki Nakagawa, Kentaro Torii, Tomoo Ogawa, Amitabh Dash, Michael Irizarry, Shobha Dhadda, Michio Kanekiyo, Steve Hersch, Takeshi Iwatsubo","doi":"10.1016/j.tjpad.2025.100160","DOIUrl":"10.1016/j.tjpad.2025.100160","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Across Asia, Alzheimer's disease prevalence is expected to rise dramatically due to, among other factors, rapidly aging populations. Alzheimer's disease pathology is triggered by the accumulation of soluble and insoluble aggregated Aβ peptides (oligomers, protofibrils, and fibrils). Lecanemab is a recently approved humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ species (oligomers, protofibrils), with activity at insoluble fibrils. In the recent 18-month phase 3 Clarity AD study, lecanemab demonstrated a consistent slowing of decline in clinical (global, cognitive, functional, and quality of life) outcomes, and reduction in brain amyloid in early Alzheimer's disease. Lecanemab was well tolerated in Clarity AD, with an increase in incidence of infusion related reactions and amyloid-related imaging abnormalities (ARIA) versus placebo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The objective of this manuscript is to present the results for the Asian region population of Clarity AD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;The core Clarity AD study was an 18-month, multicenter, double-blind, placebo-controlled, parallel-group study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Academic and clinical centers in Asia PARTICIPANTS: A total of 294 individuals with early Alzheimer's disease (i.e., mild cognitive impairment or mild Alzheimer's disease).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Intervention: &lt;/strong&gt;Eligible patients were randomized across 2 treatment groups (placebo and lecanemab 10 mg/kg biweekly) according to a fixed 1:1 schedule.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;The primary efficacy endpoint in the core study was change in the Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) from baseline at 18 months. Key secondary endpoints included change from baseline at 18 months in amyloid PET Centiloids (in patients participating in the amyloid PET sub-study), AD COMposite Score (ADCOMS) and AD Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14). Safety was monitored throughout the study in a blinded manner by the sponsor and in an unblinded manner by an independent data safety monitoring committee.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the total of 1795 subjects randomized in Clarity AD, 294 subjects were in the Asian region (Japan:152; Korea:129; Singapore:13). The efficacy of lecanemab was consistent with the overall population. For the primary endpoint, there was a slowing of decline with lecanemab in the CDR-SB at 18 months compared to placebo in the Asian region (adjusted mean difference: -0.349; 95 % confidence intervals: -0.773, 0.076; 24 % slowing of decline). Results for the secondary efficacy endpoints also favored lecanemab versus placebo in Asians. Lecanemab was well tolerated in Asian subjects, with a safety profile in Asian subjects similar to the overall Clarity AD population. The most common adverse events of special interest were ARIA-H (lecanemab:14.4 %; placebo:16.2 %), ARIA-E (lecanemab:6.2 %; placebo:1.4 %), and in","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100160"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}